Hippocampal avoidance whole-brain radiotherapy without memantine in preserving neurocognitive function for brain metastases: a phase II blinded randomized trial

• Published in: Neuro-oncology (Charlottesville, Va.) Vol. 23; no. 3; pp. 478 - 486
• Main Authors: Yang, Wen-Chi, Chen, Ya-Fang, Yang, Chi-Cheng, Wu, Pei-Fang, Chan, Hsing-Min, Chen, Jenny Ling-Yu, Chen, Guann-Yiing, Cheng, Jason Chia-Hsien, Kuo, Sung-Hsin, Hsu, Feng-Ming
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 25.03.2021
• Subjects: Brain Neoplasms - radiotherapy; Clinical Investigations; Cranial Irradiation - adverse effects; Hippocampus; Humans; Memantine - therapeutic use; Radiation Injuries; single blind method; brain metastasis; neuropsychological tests; hippocampus; whole brain radiotherapy
• ISSN: 1522-8517; 1523-5866
• DOI: 10.1093/neuonc/noaa193

Abstract Background Hippocampal avoidance whole-brain radiotherapy (HA-WBRT) shows potential for neurocognitive preservation. This study aimed to evaluate whether HA-WBRT or conformal WBRT (C-WBRT) is better for preserving neurocognitive function. Methods This single-blinded randomized phase II trial enrolled patients with brain metastases and randomly assigned them to receive HA-WBRT or C-WBRT. Primary endpoint is decline of the Hopkins Verbal Learning Test–Revised (HVLT-R) delayed recall at 4 months after treatment. Neurocognitive function tests were analyzed with a mixed effect model. Brain progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Results From March 2015 to December 2018, seventy patients were randomized to yield a total cohort of 65 evaluable patients (33 in the HA-WBRT arm and 32 in the C-WBRT arm) with a median follow-up of 12.4 months. No differences in baseline neurocognitive function existed between the 2 arms. The mean change of HVLT-R delayed recall at 4 months was −8.8% in the HA-WBRT arm and +3.8% in the C-WBRT arm (P = 0.31). At 6 months, patients receiving HA-WBRT showed favorable perpetuation of HVLT-R total recall (mean difference = 2.60, P = 0.079) and significantly better preservation of the HVLT-R recognition-discrimination index (mean difference = 1.78, P = 0.019) and memory score (mean difference = 4.38, P = 0.020) compared with patients undergoing C-WBRT. There were no differences in Trail Making Test Part A or Part B or the Controlled Oral Word Association test between the 2 arms at any time point. There were no differences in brain PFS or OS between arms as well. Conclusion Patients receiving HA-WBRT without memantine showed better preservation in memory at 6-month follow-up, but not in verbal fluency or executive function.